Age and Sex-Associated Changes of Complement Activity and Complement Levels in a Healthy Caucasian Population
Age and Sex-Associated Changes of Complement Activity and Complement Levels in a Healthy Caucasian Population
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DOI：
10.3389/fimmu.2018.02664
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发表时间：
2018-11-20
影响因子：
7.3
通讯作者：
Seelen, Marc A.
中科院分区：
文献类型：
--
作者：
da Costa, Mariana Gaya;Poppelaars, Felix;Seelen, Marc A.
补体系统对于充分的免疫反应是必不可少的。补体在疾病中的作用已经引起了很大的关注。然而，为了更好地理解补体的病理学，首先分析不同生理条件下的补体系统是至关重要的。因此，本研究的目的是调查补体活性的个体差异以及年龄和性别的影响。方法：测定120名健康志愿者的补体水平和功能活动，其中女性60名，男性60名，年龄20-69岁。以C5b-9沉积为读数，测定血清中甘露聚糖激活的经典途径（CP）、凝集素途径（mll - lp）和替代途径（AP）的血清功能活性。此外，检测C1q、MBL、MASP-1、MASP-2、ficolin-2、ficolin-3、C2、C4、C3、C5、C6、C7、C8、C9、因子B、因子D、properdin、c1抑制剂和c4b结合蛋白的水平。评估了年龄和性别相关的差异。结果：与男性相比，女性的AP活性明显降低。进一步的AP分析显示，女性的C3和适当素水平较低，而因子D浓度较高。MBL- lp活性不受性别影响，但MBL和ficolin-3水平在女性中显著低于男性。雌性和雄性之间的CP活性和CP组分无显著差异，但雌性的末端组分水平显著低于雄性。与MBL-LP活性相比，老年人的cp和AP活性明显更高。此外，c1抑制剂、C5、C8和C9随着年龄的增长而增加，而因子D和C3水平则下降。功能活性分析的深入分析表明，MBL- lp活性主要依赖于MBL和MASP-2浓度，而CP活性依赖于C2、c1抑制剂和C5水平。AP活性与C3、因子B和C5水平直接密切相关。结论：本研究显示健康人群中补体水平和功能存在显著的性别和年龄相关差异。因此，在讨论补体相关病理和随后的补体靶向治疗时，应考虑年龄和性别分析。
Introduction: The complement system is essential for an adequate immune response. Much attention has been given to the role of complement in disease. However, to better understand complement in pathology, it is crucial to first analyze this system under different physiological conditions. The aim of the present study was therefore to investigate the inter-individual variation in complement activity and the influences of age and sex.Methods: Complement levels and functional activity were determined in 120 healthy volunteers, 60 women, 60 men, age range 20-69 year. Serum functional activity of the classical pathway (CP), lectin pathway activated by mannan (MBL-LP) and alternative pathway (AP) was measured in sera, using deposition of C5b-9 as readout. In addition, levels of C1q, MBL, MASP-1, MASP-2, ficolin-2, ficolin-3, C2, C4, C3, C5, C6, C7, C8, C9, factor B, factor D, properdin, C1-inhibitor and C4b-binding protein, were determined. Age- and sex-related differences were evaluated.Results: Significantly lower AP activity was found in females compared to males. Further analysis of the AP revealed lower C3 and properdin levels in females, while factor D concentrations were higher. MBL-LP activity was not influenced by sex, but MBL and ficolin-3 levels were significantly lower in females compared to males. There were no significant differences in CP activity or CP components between females and males, nevertheless females had significantly lower levels of the terminal components. The CP. and AP activity was significantly higher in the elderly, in contrast to MBL-LP activity. Moreover, C1-inhibitor, C5, C8, and C9 increased with age in contrast to a decrease of factor D and C3 levels. In-depth analysis of the functional activity assays revealed that MBL-LP activity was predominantly dependent on MBL and MASP-2 concentration, whereas CP activity relied on C2, C1-inhibitor and C5 levels. AP activity was strongly and directly associated with levels of C3, factor B and C5.Conclusion: This study demonstrated significant sex and age -related differences in complement levels and functionality in the healthy population. Therefore, age and sex analysis should be taken into consideration when discussing complement-related pathologies and subsequent complement-targeted therapies.